Osteoporosis is a disorder of the skeleton in which bone strength is abnormally weak and susceptible to fractures from minor trauma. In the United States, about 30 million people have osteoporosis and almost 19 million more have low bone density. Current diagnostics of osteoporosis using bone density does not entirely predict fracture risk, because the internal bone structure, apart from the bone density, contributes significantly to the mechanical strength and thus fracture risk. Recent efforts have been directed toward the high-resolution three-dimensional imaging of the trabecular architecture using Magnetic Resonance Imaging (MRI) and Computed Tomography. The main MR technique (DDIF) used in this proposal is a completely new concept in bone characterization. This study proposes to use the DDIF technique to obtain statistical properties of the trabecular structure at a resolution of about 1 mu m, such as a pore size distribution, instead of high-resolution images. Preliminary work has obtained pore size distributions from bone samples and these distributions have shown a direct correlation with the mechanical properties. The long-term objective of this research is the development of new DDIF-based MR methods for in vivo evaluation of bone strength. Specific aims of the proposed research are: (1) To establish the correlation of DDIF pore size distribution with the mechanical properties of bone, (2) To develop pulse sequences to combine DDIF with MR imaging and spatial localization techniques and to quantify the accuracy of DDIF through numerical analysis. This proposal is designed to develop specific methods to incorporate DDIF into clinical MRI systems and to provide a solid evidence for the new paradigm of bone evaluation. This development will enable the next phase of the project to perform in vivo study of DDIF to further validate the method for clinical osteoporosis diagnostics and the treatment monitoring.